Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure
William M Lee, Linda S Hynan, Lorenzo Rossaro, Robert J Fontana, R Todd Stravitz, Anne M Larson, Timothy J Davern 2nd, Natalie G Murray, Timothy McCashland, Joan S Reisch, Patricia R Robuck, Acute Liver Failure Study Group, William M Lee, George A Ostapowicz, Frank V Schiødt, Julie Polson, Anne M Larson, Timothy Davern, Michael Schilsky, Timothy McCashland, J Eileen Hay, Natalie Murray, A Obaid S Shaikh, Andres Blei, Atif Zaman, Steven H B Han, Robert Fontana, Brendan McGuire, Ray Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Grace Samuel, Ezmina Lalani, Carla Pezzia, Corron Sanders, Joan Reisch, Linda Hynan, Janet P Smith, Joe W Webster, Mechelle Murry, William M Lee, Linda S Hynan, Lorenzo Rossaro, Robert J Fontana, R Todd Stravitz, Anne M Larson, Timothy J Davern 2nd, Natalie G Murray, Timothy McCashland, Joan S Reisch, Patricia R Robuck, Acute Liver Failure Study Group, William M Lee, George A Ostapowicz, Frank V Schiødt, Julie Polson, Anne M Larson, Timothy Davern, Michael Schilsky, Timothy McCashland, J Eileen Hay, Natalie Murray, A Obaid S Shaikh, Andres Blei, Atif Zaman, Steven H B Han, Robert Fontana, Brendan McGuire, Ray Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Grace Samuel, Ezmina Lalani, Carla Pezzia, Corron Sanders, Joan Reisch, Linda Hynan, Janet P Smith, Joe W Webster, Mechelle Murry
Abstract
Background & aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure.
Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation.
Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031).
Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.
Trial registration: ClinicalTrials.gov NCT00004467.
Conflict of interest statement
There are no conflicts of interest to disclose. The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy endpoints) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician who is not employed by the corporate entity. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis. This is a randomized clinical trial (ClinicalTrials.gov number NCT00004467)
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Source: PubMed